rars-1
C. elegans
putative arginine--tRNA ligase, cytoplasmic
What the model saw
Gene: rars-1 Organism: Caenorhabditis elegans Known functions: putative arginine--tRNA ligase, cytoplasmic. ATP binding. aminoacyl-tRNA ligase activity. arginine-tRNA ligase activity. nucleotide binding.
View unredacted entry
putative arginine--tRNA ligase, cytoplasmic. ATP binding. aminoacyl-tRNA ligase activity. arginine-tRNA ligase activity. nucleotide binding.
Solver output
rars-1 encodes a cytoplasmic arginine-tRNA synthetase (ArgRS), which charges tRNA with arginine and is essential for translational elongation. Aminoacyl-tRNA synthetases are rate-limiting components of the translational machinery; partial loss-of-function of translation factors in C. elegans (e.g., components of the ribosome or aminoacyl-tRNA synthetases) is well-documented to extend lifespan by reducing global protein synthesis rates, mimicking dietary restriction and dampening mTORC1/TORC1 nutrient-sensing signaling. Reduced arginine-tRNA charging would lower the aminoacylation state of tRNA-Arg, a known signal that suppresses TORC1 activity via the GCN2/AAR pathway, thereby activating stress-response and longevity programs. Additionally, arginine availability is sensed by mTORC1 through the CASTOR/SLC38A9 axis; reduced ArgRS activity could lower effective arginine utilization, further attenuating TORC1. Thus, the normal (full) function of rars-1 sustains high translational output and TORC1 activity, which is generally anti-longevity, making the gene itself pro-longevity when its activity is maintained at physiological levels to support proteostasis—but partial reduction is lifespan-extending.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model predicted "pro_longevity" but the ground truth is "anti_longevity." The model's reasoning is internally contradictory and confused. It correctly identifies that partial loss-of-function of aminoacyl-tRNA synthetases can extend lifespan in C. elegans (which would make the gene anti_longevity, since reducing its activity promotes longevity). However, the model then confusingly concludes the gene is "pro_longevity" by conflating the gene's normal function with its longevity classification. The GenAge classification of "anti_longevity" means the gene works against longevity (i.e., its normal activity shortens lifespan, and reducing it extends lifespan) — which is exactly what the model's mechanistic reasoning describes. The model essentially reasoned correctly about the mechanism but then assigned the wrong label, perhaps confused about the directionality of the GenAge classification system. The confidence of 0.62 is moderate but still wrong. The mechanism described (translation reduction extending lifespan) is plausible and consistent with the literature, but the final classification is incorrect.
Raw API responses
solver
{
"reasoning": "rars-1 encodes a cytoplasmic arginine-tRNA synthetase (ArgRS), which charges tRNA with arginine and is essential for translational elongation. Aminoacyl-tRNA synthetases are rate-limiting components of the translational machinery; partial loss-of-function of translation factors in C. elegans (e.g., components of the ribosome or aminoacyl-tRNA synthetases) is well-documented to extend lifespan by reducing global protein synthesis rates, mimicking dietary restriction and dampening mTORC1/TORC1 nutrient-sensing signaling. Reduced arginine-tRNA charging would lower the aminoacylation state of tRNA-Arg, a known signal that suppresses TORC1 activity via the GCN2/AAR pathway, thereby activating stress-response and longevity programs. Additionally, arginine availability is sensed by mTORC1 through the CASTOR/SLC38A9 axis; reduced ArgRS activity could lower effective arginine utilization, further attenuating TORC1. Thus, the normal (full) function of rars-1 sustains high translational output and TORC1 activity, which is generally anti-longevity, making the gene itself pro-longevity when its activity is maintained at physiological levels to support proteostasis—but partial reduction is lifespan-extending.",
"confidence": 0.62,
"key_pathways": [
"mTORC1/TORC1 nutrient sensing",
"GCN2-mediated amino acid sensing",
"translational regulation and protein synthesis"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The model's reasoning is internally contradictory and confused. It correctly identifies that partial loss-of-function of aminoacyl-tRNA synthetases can extend lifespan in C. elegans (which would make the gene anti_longevity, since reducing its activity promotes longevity). However, the model then confusingly concludes the gene is \"pro_longevity\" by conflating the gene's normal function with its longevity classification. The GenAge classification of \"anti_longevity\" means the gene works against longevity (i.e., its normal activity shortens lifespan, and reducing it extends lifespan) — which is exactly what the model's mechanistic reasoning describes. The model essentially reasoned correctly about the mechanism but then assigned the wrong label, perhaps confused about the directionality of the GenAge classification system. The confidence of 0.62 is moderate but still wrong. The mechanism described (translation reduction extending lifespan) is plausible and consistent with the literature, but the final classification is incorrect.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}